Cecilia Gotti - Academia.edu (original) (raw)

Papers by Cecilia Gotti

Science, Dec 17, 1982

The nicotinic acetylcholine receptor has been purified from fetal calf muscle. Amino terminal ami... more The nicotinic acetylcholine receptor has been purified from fetal calf muscle. Amino terminal amino acid sequence data indicate that the mammalian receptor is formed from closely related but distinct subunits. A cytoskeletal component, actin, may be associated with the receptor.

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, composed of fi... more Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, composed of five subunits forming a pore. The variety of receptor subtypes is mainly due to the diversity of a and b subunits encoded by at least 12 different genes (a2-10, b2-b4). ...

Journal of Immunological Methods, 1983

Fundamental & Clinical Pharmacology, 1999

Journal of Medicinal Chemistry, Sep 12, 2007

Frontiers in Molecular Neuroscience, Feb 12, 2019

British Journal of Pharmacology, Apr 19, 2017

Biochemistry, Jun 22, 1982

Nicotinic acetylcholine receptor (AcChR) was purified from fetal calf muscle by an affinity chrom... more Nicotinic acetylcholine receptor (AcChR) was purified from fetal calf muscle by an affinity chromatographic method utilizing alpha-neurotoxin from Naja naja siamensis as an immobilized ligand. Preparations of AcChR with an average specific activity of 5 nmol of alpha-toxin bound/mg of protein were obtained, i.e., 75% of the theoretical specific activity assuming identity with Torpedo AcChR. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified AcChR consistently showed the presence of five polypeptides, having apparent Mr's of 42 000, 44 000, 49 000, 55 000, and 58 000, respectively. The peptide of Mr 44K was demonstrated to be actin. The amino acid composition of fetal calf AcChR was shown to be similar to that of Torpedo AcChR. In addition, calf AcChR contained large amounts of amino sugars. The sedimentation coefficient of the purified calf AcChR was found to be 9.25 +/- 0.25, i.e., similar to the monomeric form of electric organ AcChR. Determination of the isoelectric point of alpha-bungarotoxin/calf AcChR complexes revealed the presence of two charged forms, having pI values of 5.16 +/- 0.13 and 6.05 +/- 0.18, respectively.

European Journal of Neuroscience, Feb 1, 2009

Proceedings of The Physiological Society, 2007

British Journal of Pharmacology, Feb 27, 2021

Scandinavian Journal of Gastroenterology, 2002

Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervou... more Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervous system where domains of ion channels and receptors are potential targets. The aetiology of many adult-onset conditions of severe gut dysmotility is not known. We looked for antibodies to neuronal antigens in patients with severe (slow-transit-type) constipation (STC). Eleven sera from adult-onset STC patients and 18 from childhood onset cases were tested by routine immunoprecipitation assays for antibodies against neuronal antigens including voltage-gated potassium channels (VGKCs), calcium channels (VGCCs), both muscle and neuronal acetylcholine receptor and glutamic acid decarboxylase (GAD). Results were compared with positive and negative control populations. Two of the 11 sera from patients with adult-onset STC showed highly positive anti-VGKC antibodies. Both had onset of symptoms de novo in adulthood without evidence of autoimmune, neoplastic or neurological disease. One of these patients, and one other, had anti-GAD antibodies. None of the childhood-onset STC had evidence of anti-neuronal antibodies. Anti-neuronal antibodies are found in some patients with a condition of severe acquired gut dysmotility of previously unknown aetiology. Future studies may demonstrate an autoimmune role for such antibodies.

British Journal of Pharmacology, Apr 18, 2011

Current topics in behavioral neurosciences, 2015

Nicotinic acetylcholine receptors (nAChRs) are a critical component of the brain&... more Nicotinic acetylcholine receptors (nAChRs) are a critical component of the brain's cholinergic neurotransmission system that modulates important physiological processes and whose dysfunction has been observed in patients with neurodegenerative diseases and mental illness. nAChRs are a heterogeneous family of receptor subtypes consisting of pentameric combinations of α and β subunits, and are widely expressed throughout the central and peripheral nervous system. nAChR subtypesnAChR subtypes share a common basic structure but their biophysical and pharmacological properties depend on their subunit compositionSubunit composition , which is therefore central to understanding receptor function in the nervous system and discovering new subtype-selective drugs. We briefly review some recent findings concerning the structure and function of nAChRs, particularly the native subtypes.

Journal of Neurochemistry, Jul 29, 2008

Annals of the New York Academy of Sciences, Dec 1, 1988

ChemMedChem, Apr 16, 2015

Nicotinic acetylcholine receptors (nAChRs) play an important role in many central nervous system ... more Nicotinic acetylcholine receptors (nAChRs) play an important role in many central nervous system disorders such as Alzheimer's and Parkinson's diseases, schizophrenia, and mood disorders. The α4 β2 subtype has emerged as an important target for the early diagnosis and amelioration of Alzheimer's disease symptoms. Herein we report a new class of α4 β2 receptor ligands characterized by a basic pyrrolidine nucleus, the basicity of which was properly decreased through the insertion of a fluorine atom at the 3-position, and a pyridine ring carrying at the 3-position substituents known to positively affect affinity and selectivity toward the α4 β2 subtype. Derivatives 3-(((2S,4R)-4-fluoropyrrolidin-2-yl)methoxy)-5-(phenylethynyl)pyridine (11) and 3-((4-fluorophenyl)ethynyl)-5-(((2S,4R)-4-fluoropyrrolidin-2-yl)methoxy)pyridine (12) were found to be the most promising ligands identified in this study, showing good affinity and selectivity for the α4 β2 subtype and physicochemical properties predictive of a relevant central nervous system penetration.

Science, Dec 17, 1982

The nicotinic acetylcholine receptor has been purified from fetal calf muscle. Amino terminal ami... more The nicotinic acetylcholine receptor has been purified from fetal calf muscle. Amino terminal amino acid sequence data indicate that the mammalian receptor is formed from closely related but distinct subunits. A cytoskeletal component, actin, may be associated with the receptor.

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, composed of fi... more Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, composed of five subunits forming a pore. The variety of receptor subtypes is mainly due to the diversity of a and b subunits encoded by at least 12 different genes (a2-10, b2-b4). ...

Journal of Immunological Methods, 1983

Fundamental & Clinical Pharmacology, 1999

Journal of Medicinal Chemistry, Sep 12, 2007

Frontiers in Molecular Neuroscience, Feb 12, 2019

British Journal of Pharmacology, Apr 19, 2017

Biochemistry, Jun 22, 1982

Nicotinic acetylcholine receptor (AcChR) was purified from fetal calf muscle by an affinity chrom... more Nicotinic acetylcholine receptor (AcChR) was purified from fetal calf muscle by an affinity chromatographic method utilizing alpha-neurotoxin from Naja naja siamensis as an immobilized ligand. Preparations of AcChR with an average specific activity of 5 nmol of alpha-toxin bound/mg of protein were obtained, i.e., 75% of the theoretical specific activity assuming identity with Torpedo AcChR. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified AcChR consistently showed the presence of five polypeptides, having apparent Mr's of 42 000, 44 000, 49 000, 55 000, and 58 000, respectively. The peptide of Mr 44K was demonstrated to be actin. The amino acid composition of fetal calf AcChR was shown to be similar to that of Torpedo AcChR. In addition, calf AcChR contained large amounts of amino sugars. The sedimentation coefficient of the purified calf AcChR was found to be 9.25 +/- 0.25, i.e., similar to the monomeric form of electric organ AcChR. Determination of the isoelectric point of alpha-bungarotoxin/calf AcChR complexes revealed the presence of two charged forms, having pI values of 5.16 +/- 0.13 and 6.05 +/- 0.18, respectively.

European Journal of Neuroscience, Feb 1, 2009

Proceedings of The Physiological Society, 2007

British Journal of Pharmacology, Feb 27, 2021

Scandinavian Journal of Gastroenterology, 2002

Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervou... more Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervous system where domains of ion channels and receptors are potential targets. The aetiology of many adult-onset conditions of severe gut dysmotility is not known. We looked for antibodies to neuronal antigens in patients with severe (slow-transit-type) constipation (STC). Eleven sera from adult-onset STC patients and 18 from childhood onset cases were tested by routine immunoprecipitation assays for antibodies against neuronal antigens including voltage-gated potassium channels (VGKCs), calcium channels (VGCCs), both muscle and neuronal acetylcholine receptor and glutamic acid decarboxylase (GAD). Results were compared with positive and negative control populations. Two of the 11 sera from patients with adult-onset STC showed highly positive anti-VGKC antibodies. Both had onset of symptoms de novo in adulthood without evidence of autoimmune, neoplastic or neurological disease. One of these patients, and one other, had anti-GAD antibodies. None of the childhood-onset STC had evidence of anti-neuronal antibodies. Anti-neuronal antibodies are found in some patients with a condition of severe acquired gut dysmotility of previously unknown aetiology. Future studies may demonstrate an autoimmune role for such antibodies.

British Journal of Pharmacology, Apr 18, 2011

Current topics in behavioral neurosciences, 2015

Nicotinic acetylcholine receptors (nAChRs) are a critical component of the brain&... more Nicotinic acetylcholine receptors (nAChRs) are a critical component of the brain's cholinergic neurotransmission system that modulates important physiological processes and whose dysfunction has been observed in patients with neurodegenerative diseases and mental illness. nAChRs are a heterogeneous family of receptor subtypes consisting of pentameric combinations of α and β subunits, and are widely expressed throughout the central and peripheral nervous system. nAChR subtypesnAChR subtypes share a common basic structure but their biophysical and pharmacological properties depend on their subunit compositionSubunit composition , which is therefore central to understanding receptor function in the nervous system and discovering new subtype-selective drugs. We briefly review some recent findings concerning the structure and function of nAChRs, particularly the native subtypes.

Journal of Neurochemistry, Jul 29, 2008

Annals of the New York Academy of Sciences, Dec 1, 1988

ChemMedChem, Apr 16, 2015

Nicotinic acetylcholine receptors (nAChRs) play an important role in many central nervous system ... more Nicotinic acetylcholine receptors (nAChRs) play an important role in many central nervous system disorders such as Alzheimer's and Parkinson's diseases, schizophrenia, and mood disorders. The α4 β2 subtype has emerged as an important target for the early diagnosis and amelioration of Alzheimer's disease symptoms. Herein we report a new class of α4 β2 receptor ligands characterized by a basic pyrrolidine nucleus, the basicity of which was properly decreased through the insertion of a fluorine atom at the 3-position, and a pyridine ring carrying at the 3-position substituents known to positively affect affinity and selectivity toward the α4 β2 subtype. Derivatives 3-(((2S,4R)-4-fluoropyrrolidin-2-yl)methoxy)-5-(phenylethynyl)pyridine (11) and 3-((4-fluorophenyl)ethynyl)-5-(((2S,4R)-4-fluoropyrrolidin-2-yl)methoxy)pyridine (12) were found to be the most promising ligands identified in this study, showing good affinity and selectivity for the α4 β2 subtype and physicochemical properties predictive of a relevant central nervous system penetration.